Previous studies suggest that sequential technetium-99-hydroxymethyl diphosphonate bone scanning and indium-111 leukocyte scintigraphy may play a role during revision arthroplasty. Preoperative sequential imaging was compared with joint aspiration and clinical assessment during revision knee or hip arthroplasty. Scans were considered positive if indium-111 leukocyte uptake was incongruent or focally more intense than that of technetium-99-hydroxymethyl diphosphonate uptake. Of 166 cases, 22 were infected. Sequential technetium-99-hydroxymethyl diphosphonate and indium-111 leukocyte imaging was 64% sensitive and 78% specific. Fever, physical findings, or sedimentation rate did not identify infection reliably, and preoperative aspirate culture was only 28% sensitive. Positive scintigraphy increased the likelihood of finding infection intraoperatively from 14% to 30%, although negative scintigraphy decreased this likelihood to 7%. Based on the current study, the routine use of sequential technetium-99-hydroxymethyl diphosphonate and indium-111 leukocyte imaging cannot be advocated for differentiating occult infection from mechanical failure in painful, loose total joint arthroplasties.